The likelihood of successful cancer gene therapy would be greatly enhanced by availability of a vector that could be delivered systemically and would have specific anti-tumor targeting capability along with the ability to induce death in primary and metastatic tumor cells. Vectors based on a prototype alphavirus, Sindbis virus, which were originally developed for efficient in vitro gene transfer to mammalian cells1, appear to have the desired properties2. Several factors contribute to the vectors' potential. First, in nature Sindbis virus is transmitted to mammals by mosquito bites3. After infection, the virus has a relatively long half-life in blood, and subsequently spreads to all organs of the body, including the brain4,5. Gene transfer vectors based on Sindbis virus retain the blood-borne attribute, which makes them suitable for systematic administration. Second, the surface receptor on mammalian cells for Sindbis infection has been identified as the 67-kDa high affinity laminin receptor (LAMR)6,7. LAMR has been found to be significantly upregulated in numerous human cancers8-15. Higher expression of LAMR has been related to the increasing invasiveness and malignancy of different cancers16,17. Also, in contrast to normal cells, the majority of the LAMR on cancer cells may not be occupied by laminin18,19. High levels of unoccupied LAMRs in tumor versus normal cells appear to confer on Sindbis viral vectors the ability to preferentially infect tumor cells. Third, Sindbis infection is highly apoptotic in mammalian cells20-23. Therefore the vectors themselves are sufficiently apoptotic to eliminate tumor cells that are infected.
Conventional monitoring cancer therapies include computed tomagraphy (CT), magnetic resonance imaging (MRI) and positron-emission (PET). CT requires the use of x-rays and is not suitable for pregnant patients. MRI detects the subtle differences in physiological environments, such as blood-flood, between normal and tumor tissues. In order to enhance the sensitivity and specificity, MRI for monitoring cancer therapy requires the use of contrast agents which, however, do not specifically target tumor cells. In addition, both CT and MRI are unable to detect microscopic tumors in vivo. PET, which detects the emitted radioactivity within the body, is more sensitive for monitoring cancer therapy compared with CT and NI. Recent PET technologies take advantage of the increased glucose transfer and glycolide activities in tumor cells and use a radioactive glucose homologue, 18F-fluro-2-deoxyglucose (FDG), for PET imaging. FDG is metabolized and accumulated within cells with higher glocolytic activities and produce PET signals. However, since some normal cell types also have higher glycolytic activity, such as gray matter in brain, using PET for monitoring cancer therapy in these regions is not suitable.
Therefore, what is needed in the art is improved methods for detecting cancer cells in the body or a mammal and monitoring anti-cancer therapy which overcomes the deficiencies mentioned above.